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BACKGROUND Acute kidney injury (AKI) is an important adverse outcome after major surgery. Peri-operative goal-directed haemodynamic therapy (GDT) may improve outcomes by reducing complications such as AKI. OBJECTIVE To determine if GDT was associated with a reduced incidence of postoperative AKI according to specific renal biomarkers. DESIGN Prospective substudy of the OPTIMISE trial, a multicentre randomised controlled trial comparing peri-operative GDT to usual patient care. SETTING Four UK National Health Service hospitals. PATIENTS A total of 287 high-risk patients aged at least 50 years undergoing major gastrointestinal surgery. OUTCOME MEASURES The primary outcome measure was AKI defined as urinary neutrophil gelatinase-associated lipase (NGAL) at least 150 ng ml 24 and 72 h after surgery. Secondary outcomes were between-group differences in NGAL measurements and NGAL : creatinine ratios 24 and 72 h after surgery and AKI stage 2 or greater according to Kidney Disease Improving Global Outcomes (KDIGO) criteria within 30 days of surgery. RESULTS In total, 20 of 287 patients (7%) experienced postoperative AKI of KDIGO grade 2 or 3 within 30 days. The proportion of patients with urinary NGAL at least 150 ng ml 24 or 72 h after surgery was similar in the two groups [GDT 31/144 (21.5%) patients vs. usual patient care 28/143 (19.6%) patients; P = 0.88]. Absolute values of urinary NGAL were also similar at 24 h (GDT 53.5 vs. usual patient care 44.1 ng ml; P = 0.38) and 72 h (GDT 45.1 vs. usual patient care 41.1 ng ml; P = 0.50) as were urinary NGAL : creatinine ratios at 24 h (GDT 45 vs. usual patient care 43 ng mg; P = 0.63) and 72 h (GDT 66 vs. usual patient care 63 ng mg; P = 0.62). The incidence of KDIGO-defined AKI was also similar between the groups [GDT 9/144 (6%) patients vs. usual patient care 11/143 (8%) patients; P = 0.80]. CONCLUSION In this trial, GDT did not reduce the incidence of AKI amongst high-risk patients undergoing major gastrointestinal surgery. This may reflect improving standards in usual patient care. TRIAL REGISTRATION OPTIMISE Trial Registration ISRCTN04386758.

Syphilis rates have been increasing in men who have sex with men (MSM) in London. To describe risk behaviour and refine public health interventions, we conducted prospective enhanced surveillance of new syphilis cases in MSM attending selected London sexual health clinics (SHCs) between October 2016 and January 2017. Sexual health advisors (SHAs) completed 107 questionnaires. Eighteen per cent of respondents reported always using condoms, with lower use in HIV-positive (8%, 4/53) than HIV-negative men (33%, 14/52). Almost half of respondents reported condomless sero-discordant sex (46%, 33/72). The most frequent means of meeting new partners reported were venues (80%, 76/95), particularly bars or clubs (34%, 32/95), and apps or websites (79%, 75/95). Nearly a third of respondents reported engaging in group sex (32%, 30/95). Almost half reported drug use during sex (47%, 46/98), with HIV-positive men more likely to report use of the three main ‘chemsex’ drugs. The majority of respondents preferred health promotion information from SHAs (63%, 58/92) compared to other sources such as Google/Wikipedia and apps. Prevention activity should continue to focus on condomless sex, serosorting, multiple and overlapping partners, and chemsex. SHCs, particularly those serving HIV-positive men, are important sources for sexual health promotion advice.

Background Healthcare-associated Clostridium difficile infection (CDI) in pregnant/postpartum women is underreported, especially outside of North America. We report a cluster of cases in 2 neighboring secondary care hospitals in South-East England. The objective of this study was to identify the epidemiology and risk factors for infection. Methods An investigation into a cluster of cases of confirmed CDI in pregnant/postpartum women was performed over a 12-month period, from June 2016 to June 2017. Results Eleven cases, in 10 patients, were identified, including 1 patient who had a relapse. Eight of 10 patients developed symptoms after hospital discharge. All patients had received broad-spectrum antibiotics prior to CDI onset. Environmental vectors, such as labor room mattresses, that were found difficult to effectively decontaminate after heavy contamination with blood, feces, and other body fluids may have been possible reservoirs. An infection control care bundle was successful in preventing further cases. Conclusions Antibiotic use and exposure to the organism in a contaminated labor room environment are likely risk factors for healthcare-associated CDI in postpartum women. Active surveillance is necessary to prevent these infections, as these cases often present after hospital discharge.

Background Accurate assessment of functional capacity, a predictor of postoperative morbidity and mortality, is essential to improving surgical planning and outcomes. We assessed if all 12 items of the Duke Activity Status Index (DASI) were equally important in reflecting exercise capacity. Methods In this secondary cross-sectional analysis of the international, multicentre Measurement of Exercise Tolerance before Surgery (METS) study, we assessed cardiopulmonary exercise testing and DASI data from 1455 participants. Multivariable regression analyses were used to revise the DASI model in predicting an anaerobic threshold (AT) >11 ml kg−1 min−1 and peak oxygen consumption (VO2 peak) >16 ml kg−1 min−1, cut-points that represent a reduced risk of postoperative complications. Results Five questions were identified to have dominance in predicting AT>11 ml kg−1 min−1 and VO2 peak>16 ml.kg−1min−1. These items were included in the M-DASI-5Q and retained utility in predicting AT>11 ml.kg−1.min−1 (area under the receiver-operating-characteristic [AUROC]-AT: M-DASI-5Q=0.67 vs original 12-question DASI=0.66) and VO2 peak (AUROC-VO2 peak: M-DASI-5Q 0.73 vs original 12-question DASI 0.71). Conversely, in a sensitivity analysis we removed one potentially sensitive question related to the ability to have sexual relations, and the ability of the remaining four questions (M-DASI-4Q) to predict an adequate functional threshold remained no worse than the original 12-question DASI model. Adding a dynamic component to the M-DASI-4Q by assessing the chronotropic response to exercise improved its ability to discriminate between those with VO2 peak>16 ml.kg−1.min−1 and VO2 peak Conclusions The M-DASI provides a simple screening tool for further preoperative evaluation, including with cardiopulmonary exercise testing, to guide perioperative management.

BACKGROUND: Elevated high-sensitivity troponin (hsTnT) after noncardiac surgery is associated with higher mortality, but the temporal relationship between early elevated troponin and the later development of noncardiac morbidity remains unclear. METHODS: Prospective observational study of patients aged ≥45 yr undergoing major noncardiac surgery at four UK hospitals (two masked to hsTnT). The exposure of interest was early elevated troponin, as defined by hsTnT >99th centile (≥15 ng L(−1)) within 24 h after surgery. The primary outcome was morbidity 72 h after surgery, defined by the Postoperative Morbidity Survey (POMS). Secondary outcomes were time to become morbidity-free and Clavien–Dindo ≥grade 3 complications. RESULTS: Early elevated troponin (median 21 ng L(−1) [16–32]) occurred in 992 of 4335 (22.9%) patients undergoing elective noncardiac surgery (mean [standard deviation, sd] age, 65 [11] yr; 2385 [54.9%] male). Noncardiac morbidity was more frequent in 494/992 (49.8%) patients with early elevated troponin compared with 1127/3343 (33.7%) patients with hsTnT

Contact tracing is a key part of tuberculosis prevention and care, aiming to hasten diagnosis and prevent transmission. The proportion of case-contact pairs for which recent transmission occurred and the typical timespans between the index case and their contact accessing care are not known; we aimed to calculate these. We analysed individual-level TB contact tracing data, collected in London from 20/01/2011-31/12/2015, linked to tuberculosis surveillance and MIRU-VNTR 24-locus strain-typing information. Of pairs of index cases and contacts diagnosed with active tuberculosis, 85/314 (27%) had strain typing data available for both. Of these pairs, 79% (67/85) shared indistinguishable isolates, implying probable recent transmission. Of pairs in which both contact and the index case had a social risk factor, 11/11 (100%) shared indistinguishable isolates, compared to 55/75 (75%) of pairs in which neither had a social risk factor (P = 0.06). The median time interval between the index case and their contact accessing care was 42 days (IQR: 16, 96). As over 20% of pairs did probably not involve recent transmission between index case and contact, the effectiveness of contact tracing is not necessarily limited to those circumstances where the index case has transmitted disease to their close contacts.

Historical data sources are used by a wide variety of disciplines, but rarely do they look outside their particular research fields at how others are using and applying historical data. The use and application of historical data has grown rapidly over the last couple of decades within the meteorological, geophysical and hydrological disciplines, but have done so relatively independently. By coevolving, each discipline has developed separate themes or areas, with varying degrees of uptake beyond their academic communities. We find that whilst the geophysical discipline has been relatively successful in engaging with international policymakers and stakeholders, this has not been reflected within the meteorological or hydrological disciplines to date. This disparity has occurred for a variety of reasons, including varying scales of disaster and social, political and cultural structures. In examining current developments within the disciplines, evidence suggests that this disparity is lessening, as each are using online databases and some citizen science, but that they continue to evolve independently with little unifying structure or purpose. This continued autonomy makes multi-hazard analysis challenging which, considering the potential that historical datasets present in the emerging field of multi-hazards analysis, is a considerable hindrance to this field of research. In looking forward, opportunities emerge for improved understanding of the risks presented to societies by natural hazards in the past, but also for examining how resilience, behaviour and adaptation alter during periods of repose.

Patients are living extended life with advanced cancer making it chronic rather than imminently terminal. Literature on the experience of living with advanced cancer is emerging, indicating ongoing polysymptomatic burden, lack of information, burnout (patients and caregivers), and emotional concerns, all of which contribute to emotional distress. The interdisciplinary Ottawa Palliative Rehabilitation Program (PRP) offers a scarce clinical resource for this population. The current research aimed to explore changes in self-reported distress for patients who completed the PRP, from baseline to program completion. A secondary analysis of self-report and clinical measures was performed for 180 patients who completed the PRP. Measures included the Distress Thermometer and the Problem checklists. Descriptive statistics described the sample, paired-sample t tests examined changes in Distress Thermometer scores from baseline to PRP completion, and McNemar’s tests revealed whether the most commonly endorsed checklist items changed by PRP completion. Participants (n = 180) had advanced heterogeneous cancers (mean age = 62.18, 49.4% male). From baseline to completion, significant reported changes included decreases in endorsement of clinical distress (from 55.6 to 38.9%; p

Legal norms and social behaviours are some of the human aspects surrounding the effectiveness and future of DRM security. Further exploration of these aspects would help unravel the complexities of the interaction between rights protection security and law. Most importantly, understanding the perspectives behind the circumvention of content security may have a significant impact on DRM effectiveness and acceptance at the same time. While there has been valuable research on consumer acceptability, (The INDICARE project, Bohle 2008, Akester 2009) there is hardly any work on the\ud human perspective of content creators. Taking video games as a case study, this paper employs qualitative socio-legal analysis and an interdisciplinary approach to explore this particular aspect of content protection.

Anorexia–cachexia syndrome (ACS) is a complex condition in advanced cancer patients, defined by disproportionate loss of skeletal muscle mass, and a lack or loss of appetite. This condition greatly lowers the quality of life and limits the treatment options. ACS is commonly associated with gastrointestinal symptoms such as nausea and vomiting. Ginger has been successful in treating these symptoms but has not yet been tested on patients with advanced cancer. Electrogastrography is a technology that allows the direct recording of the gastric myoelectrical activity (GMA). The aim of this study is to (1) determine the effects of ginger on the GMA in these patients, (2) evaluate the subjective symptoms using 3 validated scales, and (3) correlate the level of inflammatory factors and ghrelin in this patient population. Patients with ACS and advanced cancer were recruited from the Palliative Rehabilitation outpatient program at Elisabeth Bruyere Hospital. Patients were instructed to take a daily capsule of 1650 mg of ginger for 14 days and outcome measures were recorded at pre- and post-intervention, which included a blood test for analysis of CRP, albumin and ghrelin levels, 3 self-administered surveys (DSSI, PG-SGA, ESAS), patient-reported symptoms, and an EGG diagnosis. Fifteen patients with a median age of 58 and varying cancer diagnoses were enrolled. EGG diagnosis showed that 9 of the 15 patients had a direct improvement in their GMA, and all patients showed improvement in reported symptoms, most notably nausea, dysmotility- and reflux-like symptoms. There was no correlation found for ginger administration and inflammatory factors. These findings suggest that ginger may improve GMA as measured by EGG and may have a notable effect on symptom improvement.

Infection is a frequent cause of postoperative morbidity and mortality. The incidence, risk factors, and outcomes for postoperative infections remain poorly characterised.This is a secondary analysis of a prospective international cohort study of patients aged ≥45 yr who had noncardiac surgery (VISION), including data describing infection within 30 days after surgery. The primary outcome was postoperative infection. The secondary outcome was 30 day mortality. We used univariable and multivariable logistic regression to identify baseline risk factors for infection. Results are presented as n (%) or odds ratio (OR) with 95% confidence intervals. Some denominators vary according to rates of missing data.Among 39 996 surgical patients, 3905 (9.8%) experienced 5152 postoperative infections and 715 (1.8%) died. The most frequent infection was surgical site infection (1555/3905 [39.8%]). Infection was most strongly associated with general surgery (OR: 3.74 [3.11-4.49]; P0.01) and open surgical technique (OR: 2.03 [1.82-2.27]; P0.01); 30 day mortality was greater amongst patients who experienced infection (262/3905 [6.7%] vs 453/36 091 patients who did not [1.3%]; OR: 3.47 [2.84-4.22]; P0.01). Mortality was highest amongst patients with CNS infections (OR: 14.72 [4.41-49.12]; P0.01).Infection is a common and important complication of noncardiac surgery, which is associated with high mortality. Further research is needed to identify more effective measures to prevent infections after surgery.

IntroductionPostoperative morbidity and mortality in older patients with comorbidities undergoing gastrointestinal surgery are a major burden on healthcare systems. Infections after surgery are common in such patients, prolonging hospitalisation and reducing postoperative short-term and long-term survival. Optimal management of perioperative intravenous fluids and inotropic drugs may reduce infection rates and improve outcomes from surgery. Previous small trials of cardiac-output-guided haemodynamic therapy algorithms suggested a modest reduction in postoperative morbidity. A large definitive trial is needed to confirm or refute this and inform widespread clinical practice.MethodsThe Optimisation of Perioperative Cardiovascular Management to Improve Surgical Outcome II (OPTIMISE II) trial is a multicentre, international, parallel group, open, randomised controlled trial. 2502 high-risk patients undergoing major elective gastrointestinal surgery will be randomly allocated in a 1:1 ratio using minimisation to minimally invasive cardiac output monitoring to guide protocolised administration of intravenous fluid combined with low-dose inotrope infusion, or usual care. The trial intervention will be carried out during and for 4 hours after surgery. The primary outcome is postoperative infection of Clavien-Dindo grade II or higher within 30 days of randomisation. Participants and those delivering the intervention will not be blinded to treatment allocation; however, outcome assessors will be blinded when feasible. Participant recruitment started in January 2017 and is scheduled to last 3 years, within 50 hospitals worldwide.Ethics/disseminationThe OPTIMISE II trial has been approved by the UK National Research Ethics Service and has been approved by responsible ethics committees in all participating countries. The findings will be disseminated through publication in a widely accessible peer-reviewed scientific journal.Trial registration numberISRCTN39653756.

© 2019, The Author(s). The first large-scale water supply in Britain was not for potable domestic supplies, but for the canal network, the arteries of the industrial revolution. This paper examines how episodes of dry weather in the late eighteenth and early nineteenth centuries, reconstructed from early instrumental sources, impacted the developing canal network. Analysis reveals how a frequent lack of preparedness for even relatively minor drought events resulted in conflict between water users, with potentially serious socio-economic consequences. The economic pressure of compensating other users for loss or reduction of their water supply resulted in canal companies investing in technologies and management techniques that continue to be used today as drought mitigation strategies, such as the building of large-capacity reservoirs and groundwater abstraction. This period represents a key technological milestone in the development of the modern water supply systems, contextualising current challenges faced by the water industry in responding to drought events. Although the failure of the British canal system no longer has serious economic impacts, themes emerge from this research which are as relevant for water supplies today as they were in the eighteenth century, such as issues around water rights and the value of preparing for potential future extreme weather scenarios. A newly reconstructed composite precipitation series for Chatsworth House is presented (1760–present). Through comparing weather records within the archives of canal companies and their competitors for water supplies, historical insight can be gained into the possible far-reaching societal impacts of drought.

In October 2016, an outbreak of norovirus occurred among attendees of a Halloween-themed party at a public swimming pool in the south-east of England. Norovirus genogroup II was confirmed in 11 cases. In the retrospective cohort study of pool users, 68 individuals (37 female and 31 male), with a median age of 11 years (range: 0–50 years), met the case definition of developing diarrhoea or vomiting between 6 and 72 h after the pool visit. Multivariable analysis showed that increasing age was associated with a reduced risk of illness (odds ratio = 0.91; 95% confidence interval: 0.83–0.99). Pool behaviours (swallowing water) and the timing of visit (attending pool party after automatic dosing system was switched off) were independently associated with increased risk. Environmental investigations revealed that the automatic dosing system was switched off to reduce chlorine levels to an intended range of 0.5–1 parts per million to facilitate the use of a commercial red dye. There was a lack of compliance with the operator's own pool operating procedures, particularly on maintaining effective chlorine levels in pool water, recording of test results and recording of actions undertaken. This outbreak highlights the risks of lowering chlorine levels when using pool water colourants.

BackgroundSeveral quality of recovery (QoR) health status scales have been developed to quantify the patient’s experience after anesthesia and surgery, but to date, it is unclear what constitutes the minimal clinically important difference (MCID). That is, what minimal change in score would indicate a meaningful change in a patient’s health status?MethodsThe authors enrolled a sequential, unselected cohort of patients recovering from surgery and used three QoR scales (the 9-item QoR score, the 15-item QoR-15, and the 40-item QoR-40) to quantify a patient’s recovery after surgery and anesthesia. The authors compared changes in patient QoR scores with a global rating of change questionnaire using an anchor-based method and three distribution-based methods (0.3 SD, standard error of the measurement, and 5% range). The authors then averaged the change estimates to determine the MCID for each QoR scale.ResultsThe authors enrolled 204 patients at the first postoperative visit, and 199 were available for a second interview; a further 24 patients were available at the third interview. The QoR scores improved significantly between the first two interviews. Triangulation of distribution- and anchor-based methods results in an MCID of 0.92, 8.0, and 6.3 for the QoR score, QoR-15, and QoR-40, respectively.ConclusionPerioperative interventions that result in a change of 0.9 for the QoR score, 8.0 for the QoR-15, or 6.3 for the QoR-40 signify a clinically important improvement or deterioration.

Assessment, diagnostic criteria, management, and new therapy development in cancer – associated cachexia/anorexia are based on our understanding of the definition of this clinical problem. Efforts to define and develop diagnostic criteria for cancer cachexia are ongoing in the community of experts in clinical cancer cachexia research. Current conception of cancer cachexia underscores the central importance of skeletal muscle wasting and its consequent impairments of physical function as well as metabolic impairments (such as severe cancer treatment toxicity). Recognition of the complexity of cachexia is also of considerable importance, especially in its presentation with a variable combination of reduced food intake (with both primary and secondary etiologies) and abnormal metabolism (including tumor metabolism and host inflammation) in its underlying pathophysiology. These defining characteristics dictate a multifaceted assessment strategy focusing on muscle loss, food intake, nutrition impact symptoms, catabolic drivers including tumor burden, systemic inflammation, altered endocrine status, functional and psychosocial consequences, and estimation of survival. Cancer cachexia requires application of a multimodal therapy focusing on management of pain, other symptoms and inflammation, treatment of all reversible causes of low food intake, providing a supply of key essential nutrients, and exercise; this therapy entrains the expertise of a multidisciplinary team of health professionals as well as patients and their families.

Genotyping provides the opportunity to better understand tuberculosis (TB) transmission. We utilized strain typing data to assess trends in the proportion of clustering and identify the characteristics of individuals and clusters associated with recent United Kingdom (UK) transmission. In this retrospective cohort analysis, we included all culture-confirmed strain-typed TB notifications from the UK between 2010 and 2015 to estimate the proportion of patients that clustered over time. We explored the characteristics of patients in a cluster using multivariable logistic regression. Overall, 58.5% of TB patients were concentrated in 2,701 clusters. The proportion of patients in a cluster decreased between 2010 (58.7%) and 2015 (55.3%) (P = 0.001). Being a clustered patient was associated with being male and UK-born, having pulmonary disease, having a previous TB diagnosis, and having a history of drug misuse or imprisonment. Our results suggest that TB transmission in the UK decreased between 2010 and 2015, during which time TB incidence also decreased. Targeted cluster investigation and extended contact tracing should be aimed at persons at risk of being in a transmission chain, including UK-born individuals with social risk factors in clusters with a high proportion of patients having pulmonary disease.

Context In Canada, governments have increased spending on home care to promote better end-of-life care. In the province of Quebec, Canada, home palliative care (PC) services (HPCS) are provided by Public Local Community-Based Health Care Service providers (Centres Locaux de Services Communautaires [CLSC]) with universal coverage. Accordingly, there should be no regional variations of these services and their effect on quality of end-of-life PC (QEoLPC) indicators. Objectives To test if all the CLSCs provided the same level of HPCS to cancer patients in the province of Quebec, Canada, and the association between level of HPCS and QEoLPC indicators. Methods Characteristics of 52,316 decedents with cancer were extracted from administrative databases between 2003 and 2006. Two gender-specific "adjusted performance of CLSCs in delivering HPCS" models were created using gender-specific hierarchical regression adjusted for patient and CLSC neighborhood characteristics. Using the same approach, the strength of the association between the adjusted performance of CLSCs in delivering HPCS and the QEoLPC indicators was estimated. Results Overall, 27,255 (52.1%) decedents had at least one HPCS. Significant variations in the adjusted performance of CLSC in delivering HPCS were found. Higher performance led to a lower proportion of men having more than one emergency room visit during the last month of life (risk ratio [RR] 0.924; 95% CI 0.867–0.985), and for women, a higher proportion dying at home (RR 2.255; 95% CI 1.703–2.984) and spending less time in hospital (RR 0.765; 95% CI 0.692–0.845). Conclusion Provision of HPCS remained limited in Quebec, but when present, they were associated with improved QEoLPC indicators.

The approach to i.v. fluid therapy for hypovolaemia may significantly influence outcomes for patients who experience a systemic inflammatory response after sepsis, trauma, or major surgery. Currently, there is no single i.v. fluid agent that meets all the criteria for the ideal treatment for hypovolaemia. The physician must choose the best available agent(s) for each patient, and then decide when and how much to administer. Findings from large randomized trials suggest that some colloid-based fluids, particularly starch-based colloids, may be harmful in some situations, but it is unclear whether they should be withdrawn from use completely. Meanwhile, crystalloid fluids, such as saline 0.9% and Ringer's lactate, are more frequently used, but debate continues over which preparation is preferable. Perhaps most importantly, it remains unclear how to select the optimal dose of fluid in different patients and different clinical scenarios. There is good reason to believe that both inadequate and excessive i.v. fluid administration may lead to poor outcomes, including increased risk of infection and organ dysfunction, for hypovolaemic patients. In this review, we summarize the current knowledge on this topic and identify some key pitfalls and some areas of agreed best practice.

Physicians embrace the concept of rehabilitation, but may think of it only as it relates to restoring function through exercise. We use a broader definition that applies to patients with advanced cancer. Cancer rehabilitation is a process that assists a person with a cancer diagnosis to obtain

Background: Myocardial injury after noncardiac surgery (MINS) was defined as prognostically relevant myocardial injury due to ischemia that occurs during or within 30 days after noncardiac surgery. The study’s four objectives were to determine the diagnostic criteria, characteristics, predictors, and 30-day outcomes of MINS. Methods: In this international, prospective cohort study of 15,065 patients aged 45 yr or older who underwent in-patient noncardiac surgery, troponin T was measured during the first 3 postoperative days. Patients with a troponin T level of 0.04 ng/ml or greater (elevated “abnormal” laboratory threshold) were assessed for ischemic features (i.e., ischemic symptoms and electrocardiography findings). Patients adjudicated as having a nonischemic troponin elevation (e.g., sepsis) were excluded. To establish diagnostic criteria for MINS, the authors used Cox regression analyses in which the dependent variable was 30-day mortality (260 deaths) and independent variables included preoperative variables, perioperative complications, and potential MINS diagnostic criteria. Results: An elevated troponin after noncardiac surgery, irrespective of the presence of an ischemic feature, independently predicted 30-day mortality. Therefore, the authors’ diagnostic criterion for MINS was a peak troponin T level of 0.03 ng/ml or greater judged due to myocardial ischemia. MINS was an independent predictor of 30-day mortality (adjusted hazard ratio, 3.87; 95% CI, 2.96–5.08) and had the highest population-attributable risk (34.0%, 95% CI, 26.6–41.5) of the perioperative complications. Twelve hundred patients (8.0%) suffered MINS, and 58.2% of these patients would not have fulfilled the universal definition of myocardial infarction. Only 15.8% of patients with MINS experienced an ischemic symptom. Conclusion: Among adults undergoing noncardiac surgery, MINS is common and associated with substantial mortality.

Background: Cancer can affect many dimensions of a patient’s life, and in turn, it should be targeted using a multimodal approach. We tested the extent to which an interdisciplinary nutrition–rehabilitation program can improve the well-being of patients with advanced cancer. Methods: Between January 10, 2007, and September 29, 2010, 188 patients with advanced cancer enrolled in the 10–12-week program. Body weight, physical function, symptom severity, fatigue dimensions, distress level, coping ability, and overall quality of life were assessed at the start and end of the program. Results: Of the enrolled patients, 70% completed the program. Patients experienced strong improvements in the physical and activity dimensions of fatigue (effect sizes: 0.8–1.1). They also experienced moderate reductions in the severity of weakness, depression, nervousness, shortness of breath, and distress (effect sizes: 0.5–0.7), and moderate improvements in Six Minute Walk Test distance, maximal gait speed, coping ability, and quality of life (effect sizes: 0.5–0.7) Furthermore, 77% of patients either maintained or increased their body weight. Conclusions: Interdisciplinary nutrition–rehabilitation can be advantageous for patients with advanced cancer and should be considered an integrated part of standard palliative care.

Background: For evidence-based medical practice, well-defined risk scoring systems are essential to identify patients with a poor prognosis. The objective of this study was to develop a prognostic score, the Montreal prognostic score (MPS), to improve prognostication of patients with incurable non-small cell lung cancer (NSCLC) in everyday practice. Methods: A training cohort (TC) and a confirmatory cohort (CC) of newly diagnosed patients with NSCLC planning to receive chemotherapy were used to develop the MPS. Stage and clinically available biomarkers were entered into a Cox model and risk weights were estimated. C-statistics were used to test the accuracy. Results: The TC consisted of 258 patients and the CC consisted of 433 patients. Montreal prognostic score classified patients into three distinct groups with median survivals of 2.5 months (95% confidence interval (CI): 1.8, 4.2), 8.2 months (95% CI: 7.0, 9.4) and 18.2 months (95% CI: 14.0, 27.5), respectively (log-rank, P

This study uses extended (1880s–2012) rainfall series to examine the implications of historical droughts on water supply yield calculations used in water resource management and drought planning across the English Midlands and Central Wales. UK guidance to water companies is to use climate data from the 1920s to present where possible in modelling to inform water resource management and drought plans; but this period excludes several significant droughts of the late 19th century. This study uses the standardised precipitation index and hydrological modelling (HYSIM and AQUATOR) to investigate the implications of pre-1920s droughts on water resource management. Although drought characterisation identifies two significant droughts in the pre-1920 period, the impact of these events on reservoir storage is less severe than droughts identified in the post-1920 period, indicating that the use of long climate series in water resource modelling is a valuable tool in assessing the robustness of current water resource modelling used in the water resource sector.

This article reviews the current status of the definition of cancer cachexia, and comments on future initiatives to refine it and to use it as a foundation for a cancer cachexia classification system.There has been a plethora of work by expert panels defining cachexia. Stemming from this work, an expert panel has published a definition of cancer cachexia and a three level staging system: precachexia, cachexia, and refractory cachexia. Colleagues in the cancer pain field have put forward a sophisticated pain classification system. Work to develop a similar classification system for cachexia is now commencing. Aside from improved communication, these efforts may also enable the oncology community to better appreciate the importance of cancer cachexia and to participate in interdisciplinary treatment programmes to combat cachexia.The quest to determine the pathophysiology of cancer cachexia and to use this knowledge to identify patient subsets will further research. Equally important, the fruits of this endeavour will lead to a higher priority for addressing cachexia with consequent development of a multimodal approach to management.

BACKGROUND A pilot study (NCT00316563) to determine if delta-9-tetrahydrocannabinol (THC) can improve taste and smell (chemosensory) perception as well as appetite, caloric intake, and quality of life (QOL) for cancer patients with chemosensory alterations. PATIENTS AND METHODS Adult advanced cancer patients, with poor appetite and chemosensory alterations, were recruited from two sites and randomized in a double-blinded manner to receive either THC (2.5 mg, Marinol(®); Solvay Pharma Inc., n = 24) or placebo oral capsules (n = 22) twice daily for 18 days. Twenty-one patients completed the trial. At baseline and posttreatment, patients completed a panel of patient-reported outcomes: Taste and Smell Survey, 3-day food record, appetite and macronutrient preference assessments, QOL questionnaire, and an interview. RESULTS THC and placebo groups were comparable at baseline. Compared with placebo, THC-treated patients reported improved (P = 0.026) and enhanced (P < 0.001) chemosensory perception and food 'tasted better' (P = 0.04). Premeal appetite (P = 0.05) and proportion of calories consumed as protein increased compared with placebo (P = 0.008). THC-treated patients reported increased quality of sleep (P = 0.025) and relaxation (P = 0.045). QOL scores and total caloric intake were improved in both THC and placebo groups. CONCLUSIONS THC may be useful in the palliation of chemosensory alterations and to improve food enjoyment for cancer patients.

This paper details the CFD validation studies carried out as a prerequisite for multi-fidelity CFD-based design optimization of high-speed passenger-only ferries aimed at reducing far-field wake energy that causes beach erosion. A potential flow program (WARP) and a URANS program (CFDSHIP) were validated using full-scale measurements of resistance, sinkage, trim, and far-field wake train obtained over a wide range of speeds for two high-speed semi-planing foil-assisted catamarans: Spirit (LOA-22 m) and 1060 (LOA-17 m). This study posed a unique combination of challenges for CFD modeling: the foil appended geometry required complicated surface overset grids, the effect of the waterjet and wind resistance had to be modeled, and a method had to be devised to extrapolate the calculated near-field elevation to get the far-field wake train using Havelock sources. A more concentrated effort was applied to the URANS verification and validation which forms the focus of this paper. The results show that URANS is able to accurately predict the resistance and motions for both vessels when coupled with models that account for the propulsors and air resistance. The overall accuracy of URANS for the performance analysis of the foil-assisted, semi-planing catamarans was adequate to warrant its use as a tool for subsequent design and optimization of a new vessel with significantly reduced wakes.

The wakes of high-speed passenger-only ferries that operated through Rich Passage, on the Seattle-Bremerton ferry route, caused beach erosion and damage to habitat. A task was initiated to design a low-wake high-speed vessel using multi-fidelity CFD based design optimization by using low-fidelity potential flow solvers for initial global design optimization and by using URANS solvers for high-fidelity tuning of the optimized design. This simulation based design process involved a close collaboration between ship designers, and hydrodynamics and CFD specialists, whose collective expertise guided the evolution of the design based on both hydrodynamic and structural aspects. The initial hull shape optimization using potential flow code was carried out by blending three different initial concepts provided by the designers. Subsequently, URANS was used to evaluate the potential flow optimized hull and to further optimize the hull configuration parameters, namely, the centre-of-gravity, demihull spacing, foil location, foil angle and slenderness ratio at different displacement conditions. The URANS based configuration optimization also took into account the far field wakes' energy spectrum with an objective of reducing the energetic, low frequency far field wakes which are associated with beach flattening on the mixed sand and gravel beaches. Calculation of the far field wake using URANS would require an unfeasibly large domain size; therefore, a Havelock code with a source distribution matching the URANS calculated near field wave elevation was used to propagate the wakes into the far field. The end result of the optimization was a design with significantly reduced far field wake, which is currently being built for experimental testing.

The Society for Sarcopenia, Cachexia, and Wasting Disease convened an expert panel to develop nutritional recommendations for prevention and management of sarcopenia. Exercise (both resistance and aerobic) in combination with adequate protein and energy intake is the key component of the prevention and management of sarcopenia. Adequate protein supplementation alone only slows loss of muscle mass. Adequate protein intake (leucine-enriched balanced amino acids and possibly creatine) may enhance muscle strength. Low 25(OH) vitamin D levels require vitamin D replacement.

Background: C-reactive protein (CRP) is gaining credibility as a prognostic factor in different cancers. Cox's proportional hazard (PH) model is usually used to assess prognostic factors. However, this model imposes a priori assumptions, which are rarely tested, that (1) the hazard ratio associated with each prognostic factor remains constant across the follow-up (PH assumption) and (2) the relationship between a continuous predictor and the logarithm of the mortality hazard is linear (linearity assumption). Methods: We tested these two assumptions of the Cox's PH model for CRP, using a flexible statistical model, while adjusting for other known prognostic factors, in a cohort of 269 patients newly diagnosed with non-small cell lung cancer (NSCLC). Results: In the Cox's PH model, high CRP increased the risk of death (HR=1.11 per each doubling of CRP value, 95% CI: 1.03–1.20, P=0.008). However, both the PH assumption (P=0.033) and the linearity assumption (P=0.015) were rejected for CRP, measured at the initiation of chemotherapy, which kept its prognostic value for approximately 18 months. Conclusion: Our analysis shows that flexible modeling provides new insights regarding the value of CRP as a prognostic factor in NSCLC and that Cox's PH model underestimates early risks associated with high CRP.

Distress is defined by the National Comprehensive Cancer Network as a multifactorial unpleasant emotional experience of a psychological, social, and/or spiritual nature that may interfere with the ability to cope effectively with cancer. We investigated the prevalence and associated symptoms of distress in newly diagnosed lung cancer patients.Between November 2005 and July 2007, 98 newly diagnosed lung cancer patients completed an assessment. The Distress Thermometer (DT) and Edmonton Symptom Assessment Scale (ESAS) were used as screening tools.Fifty (51%) patients reported clinically significant distress (or=4) on the DT. Of those, 26 (52%) patients reported high levels of depression, nervousness, or both on ESAS. The remaining 24 (48%) patients had elevated levels of distress but no significant depression or nervousness. A correlation between the DT and the total ESAS score was observed (Pearson correlation = 0.46). The ten items of the ESAS together explained 46% of the variability in DT scores. The depression and nervousness ESAS items were significant predictors of DT score (p0.01 for both items). However, once the two psychosocial items, depression and nervousness, were removed from the total ESAS score, leaving only physical symptoms and the sleeplessness item, the predictive power of the model decreased to R(2) = 0.12.The prevalence of distress in lung cancer patients is high. The DT appears to discriminate between physical and emotional distress. This easily measured score may determine which patients require further intervention for emotional distress.

The regulation of cutaneous immune responses in health and disease is mediated locally by proteins such as cytokines and chemokines. We used a novel approach involving proteomic profiling of fluid drawn from suction blisters to compare and contrast protein expression in normal skin with that in nonlesional skin from a patient with plaque psoriasis. We also examined the impact of exogenous interleukin-1beta, a proinflammatory cytokine, on protein expression in these tissues. Described here are the results of proteomic profiling of 670 proteins from blister fluid, and the identification by differential expression of nine proteins between one volunteer with psoriasis and one normal volunteer. Although the apparent disease association of these nine proteins will require validation using additional volunteers, the identification of candidate protein biomarkers through proteomic analyses of blister fluid represents a promising approach for monitoring the disease activity and efficacy of therapeutic intervention in human skin diseases.

Background Stroke volume variation (SVV) and pulse pressure variation (PPV), termed dynamic markers of preload responsiveness, may predict the response to i.v. fluid in critically ill patients. However, the predictive accuracy of these variables during gastrointestinal surgery remains uncertain. Methods Observational study of patients aged ≥50 yr undergoing major gastrointestinal surgery, enrolled in the OPTIMISE trial. Patients received six 250 ml fluid challenges with i.v. colloid solution (three during and three after surgery), while SVV and PPV were measured using the LiDCOrapid monitor (LiDCO Ltd, UK). Fluid responsiveness was defined as a stroke volume increase ≥10%. Area under the receiver operating characteristic curve was calculated with 95% confidence intervals. Adjustment for covariates was performed by regression modelling and a clustering method was used to adjust for intra-patient correlation. Results One hundred patients were recruited between August 2010 and October 2012. Five hundred and fifty-six fluid challenges were administered and 159 (28.6%) were associated with increased stroke volume. The predictive value of both variables was poor during surgery [SVV 0.69 (0.63–0.77); PPV 0.70 (0.62–0.77)], and also after surgery [SVV 0.69 (0.63–0.78); PPV 0.64 (0.56–0.73)]. The findings were similar when analysed according to whether patients were mechanically ventilated [SVV 0.68 (0.63–0.77); PPV 0.69 (0.61–0.77)] or breathing spontaneously [SVV 0.69 (0.61–0.77); PPV 0.63 (0.56–0.72)]. Predictive value improved slightly in a sensitivity analysis excluding outlier values of SVV and PPV. Conclusions In this study, the predictive accuracy of SVV and PPV for fluid responsiveness was insufficient to recommend for routine clinical use during or after major gastrointestinal surgery.

Palliative care is no longer solely an excercise in controlling suffering at the end of life. If we are to apply the principles of palliative care throughout the course of illness, both the culture and the organization of palliative care services must change. New partners must be enlisted in more sophisticated, increasingly academic partnerships. This change, while welcome and necessary, must come about with perservation of the core values of palliative care.

Mrs MJ is a 56-year-old architect with a husband and two children. You performed a mastectomy and axillary dissection on her after neoadjuvant chemotherapy for locally advanced breast cancer 2 years ago. Unfortunately, she developed widespread disease with metastases to liver, lung, and bone. After several more rounds of chemotherapy, she is currently on antiestrogen therapy. Her disease appears stable. You have continued to follow her and she comes to see you for her routine visit. You notice that she is much thinner than you remember, but otherwise looks well. You ask her about her weight loss. She says: “I don’t really know what it is! I can eat, my bowels are working, but I simply don’t want to. I force myself to swallow food, but I keep losing weight anyway.” On clinical examination, you notice her muscle wasting and recognize the signs of cancer cachexia. You want to know more about how to manage this phenomenon.

Graduating medical students from the class of 1999 from McGill University and the University of Alberta completed a self-administered, anonymous, pilot survey to determine students' perspectives on how their educational experience in common palliative care topics contrasted with their educational experience in the diagnosis and management of hypertension, non palliative aspects of breast cancer, and patients dying of acquired immune deficiency syndrome (AIDS).A Likert scale ranging from "excellent," scored 1, "very poor," scored 5, was used. Students also estimated the number of hours they spent, during their training, in operating rooms, on home visits to terminally ill patients, and in interprofessional teaching.Sixty of 114 (53%) students from McGill University, and 53 of 110 (48%) students from the University of Alberta responded to the survey. The mean ratings of education experience in the various topics for both universities combined were as follows: hypertension, 2.03; breast cancer, 2.33; cancer pain, 3.42; communicating with dying patients, 3.32; and caring for patients with AIDS, 4.15. The average number of hours spent in the operating room, on home visits to terminally patients, and in interprofessional teaching for both universities combined were 155 hours, 4.2 hours, and 16 hours, respectively. Of the responding students from both universities 83% favored increased palliative care teaching.Despite the disproportionate number of hours spent in operating rooms compared to palliative care community exposure, only two students, one from each university, favored shortening surgical rotations to allow for increased time for palliative care education. Recommendations, including increasing palliative care education during clinical clerkships, are provided to improve medical students' perceptions of their educational experiences in palliative care education.

We report the results of a cancer pain survey mailed to Quebec hematologist-oncologists and palliative care physicians in 1999. The survey was designed to sample views on the current status of pain management and on obstacles to the provision of adequate pain relief for patients. The survey, formulated by an ethics network centered at the Clinical Research Institute of Montreal, was distributed to all members of the Association of Hematologist-Oncologists of Quebec and to all physician members of the Quebec Palliative Care Association. Responses were obtained from 138 Palliative Care Association members (response rate 61%) and 76 hematologist-oncologists (response rate 45%). Major obstacles reported included inadequate assessment of both contributory psychosocial issues and severity of pain, patient reluctance to take opioids, and inadequate access to non-drug techniques for pain relief. Access to opioids was not regarded as a problem. Both groups felt generally competent in their ability to manage various aspects of cancer pain therapy. They gave little credit to their formal medical school or residency training. Fifty-six percent of the palliative care group and 57% of the hemato-oncologists rated their medical school experience as only "poor" or "fair" on a 4-point scale. Residency ratings were modestly better. We conclude that medical faculties should assign a high priority to teaching health professionals patient assessment techniques. Simple symptom assessment scales should be routinely used in oncology/palliative care practice. Medical school training in pain management is not highly regarded and should be enhanced. We also note that, based on response to the scenario of a patient presenting with severe pain, many physicians, while feeling competent in the use of opioids, may be overly conservative in their initial use.

Losing streams that are influenced by wastewater treatment plant effluents and combined sewer overflows (CSOs) can be a source of groundwater contamination. Released micropollutants such as pharmaceuticals, endocrine disrupters and other ecotoxicologically relevant substances as well as inorganic wastewater constituents can reach the groundwater, where they may deteriorate groundwater quality. This paper presents a method to quantify exfiltration mass flow rates per stream length unit Mex of wastewater constituents from losing streams by the operation of integral pumping tests (IPTs) up- and downstream of a target section. Due to the large sampled water volume during IPTs the results are more reliable than those from conventional point sampling. We applied the method at a test site in Leipzig (Germany). Wastewater constituents K+ and NO3− showed Mex values of 1241 to 4315 and 749 to 924 mg mstream−1 d−1, respectively, while Cl− (16.8 to 47.3 g mstream−1 d−1) and SO42− (20.3 to 32.2 g mstream−1 d−1) revealed the highest observed Mex values at the test site. The micropollutants caffeine and technical-nonylphenol were dominated by elimination processes in the groundwater between upstream and downstream wells. Additional concentration measurements in the stream and a connected sewer at the test site were performed to identify relevant processes that influence the concentrations at the IPT wells. ISSN:1812-2116 ISSN:1812-2108

After treatment, patients with active cancer face a considerable burden from the effects of both the disease and its treatment. The Palliative Rehabilitation Program (prp) is designed to ameliorate disease effects and to improve the patient&rsquo, s functioning. The present study evaluated predictors of program completion and changes in functioning, symptoms, and well-being after the program. The program received referrals for 173 patients who had finished anticancer therapy. Of those 173 patients, 116 with advanced cancer were eligible and enrolled in the 8-week interprofessional prp, 67 completed it. Measures of physical, nutritional, social, and psychological functioning were evaluated at entry to the program and at completion. Participants experienced significant improvements in physical performance (p < 0.000), nutrition (p = 0.001), symptom severity (p = 0.005 to 0.001), symptom interference with functioning (p = 0.003 to 0.001), fatigue (p = 0.001), and physical endurance, mobility, and balance or function (p = 0.001 to 0.001). Reasons that participants did not complete the prp were disease progression, geographic inaccessibility, being too well (program not challenging enough), death, and personal or unknown reasons. A normal level of C-reactive protein (

Today, most oncologists would agree that Anderson’s statement is common sense and subscribe to its expressed wisdom. [...]

The authors of this paper are the three General Lighthouse Authorities (GLAs) of the United Kingdom and the Republic of Ireland. It was presented on their behalf at the RIN-96 conference by Captain Turner. The paper gives a brief overview of the policy of the GLAs (i.e. the Corporation of Trinity House, the Northern Lighthouse Board and the Commissioners of Irish Lights) regarding the provision of an aids to navigation service with emphasis on the future prospects of traditional aids to navigation over the next 25 years. The three GLAs have recently carried out a consultation exercise on marine aids to navigation into the 21st century. The results of this consultation exercise are discussed. It should be noted that, for clarity, the General Lighthouse Authorities (GLAs) refer to the systems that they provide as ‘aids to navigation’ (AtoN), to differentiate their provision from the equipment carried on board ships for navigational purposes which are referred to by the GLAs as ‘navigational aids’. This paper therefore in the main deals with AtoN.The coastlines within the GLAs' areas of responsibility rank with the most heavily trafficked and dangerous in the world. The coastlines vary from isolated rocks and the steep, Atlantic coastline, to the low-lying relatively featureless coastline of south-east England, off which are shifting sandbanks and channels. The tidal range in GLA waters is significant and tidal streams can reach 10 knots or more in a number of places.

peer-reviewed Context. Delirium occurs commonly in settings of palliative care (PC), in which patient vulnerability in the unique context of end-of-life care and delirium-associated impairment of decision-making capacity may together present many ethical challenges.Objectives. Based on deliberations at the Studies to Understand Delirium in Palliative Care Settings (SUNDIPS) meeting and an associated literature review, this article discusses ethical issues central to the conduct of research on delirious PC patients.Methods. Together with an analysis of the ethical deliberations at the SUNDIPS meeting, we conducted a narrative literature review by key words searching of relevant databases and a subsequent hand search of initially identified articles. We also reviewed statements of relevance to delirium research in major national and international ethics guidelines.Results. Key issues identified include the inclusion of PC patients in delirium research, capacity determination, and the mandate to respect patient autonomy and ensure maintenance of patient dignity. Proposed solutions include designing informed consent statements that are clear, concise, and free of complex phraseology; use of concise, yet accurate, capacity assessment instruments with a minimally burdensome schedule; and use of PC friendly consent models, such as facilitated, deferred, experienced, advance, and proxy models.Conclusion. Delirium research in PC patients must meet the common standards for such research in any setting. Certain features unique to PC establish a need for extra diligence in meeting these standards and the employment of assessments, consent procedures, and patient-family interactions that are clearly grounded on the tenets of PC. (C) 2014 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved. peer-reviewed

Purpose Emerging evidence suggests muscle depletion predicts survival of patients with cancer. Patients and Methods At a cancer center in Alberta, Canada, consecutive patients with cancer (lung or GI; N = 1,473) were assessed at presentation for weight loss history, lumbar skeletal muscle index, and mean muscle attenuation (Hounsfield units) by computed tomography (CT). Univariate and multivariate analyses were conducted. Concordance (c) statistics were used to test predictive accuracy of survival models. Results Body mass index (BMI) distribution was 17% obese, 35% overweight, 36% normal weight, and 12% underweight. Patients in all BMI categories varied widely in weight loss, muscle index, and muscle attenuation. Thresholds defining associations between these three variables and survival were determined using optimal stratification. High weight loss, low muscle index, and low muscle attenuation were independently prognostic of survival. A survival model containing conventional covariates (cancer diagnosis, stage, age, performance status) gave a c statistic of 0.73 (95% CI, 0.67 to 0.79), whereas a model ignoring conventional variables and including only BMI, weight loss, muscle index, and muscle attenuation gave a c statistic of 0.92 (95% CI, 0.88 to 0.95; P < .001). Patients who possessed all three of these poor prognostic variables survived 8.4 months (95% CI, 6.5 to 10.3), regardless of whether they presented as obese, overweight, normal weight, or underweight, in contrast to patients who had none of these features, who survived 28.4 months (95% CI, 24.2 to 32.6; P < .001). Conclusion CT images reveal otherwise occult muscle depletion. Patients with cancer who are cachexic by the conventional criterion (involuntary weight loss) and by two additional criteria (muscle depletion and low muscle attenuation) share a poor prognosis, regardless of overall body weight.

A 39-year-old woman with breast cancer metastatic to bone presented with acute hip pain marginally responsive to escalating doses of opioid analgesics. Pathologic pelvic fractures were present and there were minimal clinical indicators of infection, but the severity and intractable nature of the pain prompted further investigation. Computed tomography revealed a pelvic abscess. Antibiotic therapy and drainage of the abscess resulted in markedly improved pain control, decreased analgesic requirements, and improved quality of life. We suggest that, in patients with malignancy, the diagnosis of occult infection should be aggressively pursued as a potentially reversible cause of intractable pain.

The National Cancer Institute (Canada) sponsored a workshop on symptom control in Banff, Alberta, in October 1993. This article reports on the workshop recommendations for research on one symptom complex, the cachexia-anorexia-asthenia syndrome. In addition to encouraging study generation, the recommendations provide a baseline for assessing the scope and strength of future Canadian research initiatives on cachexia-anorexia-asthenia.

Palliative care is now an integral part of the undergraduate medical curriculum. Medical education across the board is adopting a case-based approach. This book uses a series of cases to illustrate critical points in palliative medicine. The case-studies have been carefully chosen to reflect real life clinical practice. The chapters illustrate, through the case studies, the desired skills, attitudes, and knowledge required in this field of medicine. Since publication of the second edition, many approaches to palliative care have been further refined and developed. Ongoing research has led to the improved use of existing medications, and the development of several new treatments. More is known about the psychosocial existential distress experienced by patients and their families resulting in an improved understanding by health care providers of how best to approach and assist those affected by advanced illness, and more is known about methadone and other medications with emerging uses. The third edition of this book continues to offer a panoramic view of palliative care. It introduces a number of new topics including neurological disorders, the last days, and palliative sedation.